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Quinazoline compound and preparation method and application thereof

A compound, quinazoline technology, applied in the direction of organic chemical methods, chemical instruments and methods, isotope introduction into organic compounds, etc., can solve the problems of low radiochemical yield, insufficient tumor selectivity, complex and cumbersome preparation, etc.

Active Publication Date: 2019-02-01
SHANGHAI INST OF APPLIED PHYSICS - CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] The technical problem to be solved by the present invention is to overcome the problems that the existing PET imaging agents targeting EGFR are not high enough for tumor selectivity, the radiochemical yield is low, and the preparation is complicated and cumbersome, and a quinazoline compound, its Preparation method and application

Method used

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  • Quinazoline compound and preparation method and application thereof
  • Quinazoline compound and preparation method and application thereof
  • Quinazoline compound and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0067] Embodiment 1: the synthesis of I-1

[0068] (1) 100mCi 18 f - By quaternary ammonium type anion column QMA (the product of American Waters company, 18 f - Provided by Kexing Pharmaceutical Co., Ltd.) after capture, take 2mL K 222 (i.e. Kryptofix 222) solution (28.8mg K 222 , 6.0 mg K 2 CO 3 , 1920μL acetonitrile, 80μL water solution) will 18 Rinse F into the reaction bottle, immerse the reaction bottle in an oil bath at 95°C, dry it with nitrogen, then add 500 μL of anhydrous acetonitrile to dry it, repeat the drying with anhydrous acetonitrile twice;

[0069] (2) 500 μL of anhydrous acetonitrile solution containing 5 mg 2-azidoethyl p-toluenesulfonate was rapidly added to the solution containing K 222 、K 2 CO 3 and 18 f - In the mixture, stop the reaction after closed reaction at 95°C for 10 minutes, and cool in an ice-water bath to obtain compound C1-1, and the labeling rate can reach more than 97%;

[0070]

[0071] (3) The reaction liquid containing ...

Embodiment 2

[0075] Embodiment 2: the synthesis of I-1

[0076] (1) 40mCi 18 f - By quaternary ammonium type anion column QMA (the product of American Waters company, 18 f - Provided by Shanghai Kexing Pharmaceutical Co., Ltd.) after capture, take 1.0mL K 222 (i.e. Kryptofix 222) solution (14.4mg K2.2.2, 3.0mgK 2 CO 3 , 960μL acetonitrile, 40μL water solution) will 18 f - Rinse into the reaction bottle, immerse the reaction bottle in a 95°C oil bath, blow dry with nitrogen, then add 500 μL of anhydrous acetonitrile to dry, repeat the above operation twice;

[0077] (2) 400 μL of anhydrous dimethylformamide solution containing 5 mg 2-azidoethyl p-toluenesulfonate was rapidly added to the solution containing K 222 、K 2 CO 3 and 18 f - In the mixture, stop the reaction after closed reaction at 100°C for 5 minutes, and cool in an ice-water bath to obtain compound C1-1, and the labeling rate can reach more than 98%;

[0078]

[0079] (3) Add 500 μL of acetonitrile to the reactio...

Embodiment 3

[0083] Embodiment 3: the synthesis of I-2

[0084] (1) 4.23g 2-fluoroethyl-4 methylbenzenesulfonate and 3.78g sodium azide were reacted at room temperature in DMF for 12h, and the DMF solution of C2-1 was obtained after the solid was removed by filtration. The product was not further purified and directly for subsequent reactions;

[0085]

[0086] (2) Add 200 uL each of 0.5 mol / L copper sulfate and 1.5 mol / L sodium ascorbate to 6 mL of PBS (PH=6), then add 26.7 mg of icotinib and 2 mL of the above-mentioned C2-1 in DMF, 50 ℃ water bath reaction for 1h. The product was diluted with water, extracted with ethyl acetate, dried, and concentrated under reduced pressure to remove ethyl acetate to obtain product I-2 with a yield of 96%.

[0087]

[0088] The identification data of I-2 are as follows:

[0089] MS(ESI):M(C 24 h 25 FN 6 o 4 )=480.49(m / z),[M+H] + 481.15,[M+Na] + 503.15.

[0090] 1 H-NMR (400MHz, CD 3 OD):δ8.65(s,1H),8.54(s,1H),8.34(s,1H),8.22(s,1H),7.93...

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Abstract

The invention discloses a quinazoline compound and a preparation method and application thereof. The quinazoline compound as a medical developer has stable structure and high developing resolution. The preparation method is simple to perform, has short reaction time and high radioactive chemical yield and is easy to apply to industrial large-scale production.

Description

technical field [0001] The present invention relates to a quinazoline compound, its preparation method and application. Background technique [0002] Lung cancer is the number one cancer killer in the world. In recent years, the incidence rate has continued to rise globally, especially in China. According to the "China Tumor Registration Annual Report", in 2012, lung cancer has replaced liver cancer as the first cause of death from malignant tumors in my country, accounting for 22.7% of all malignant tumor deaths. From 1988 to 2005, the average annual growth rate of lung cancer incidence in my country was 1.63%. If effective control measures are not taken in time, it is estimated that by 2025, my country will become the world's largest lung cancer incidence country (Hao Jie, Chen Wanqing. 2012 China Cancer Registration Annual Report [M] . Military Medical Science Press, 2012. Yao Xiaojun, Liu Lunxu. Epidemiology and treatment status of lung cancer [J]. Modern Oncology, 2014,...

Claims

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Application Information

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IPC IPC(8): C07D491/056C07B59/00
CPCC07B59/002C07B2200/05C07D491/056
Inventor 贾丽娜芦鑫淼张岚
Owner SHANGHAI INST OF APPLIED PHYSICS - CHINESE ACAD OF SCI
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